The DOI matches its Crossref record.
Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHD
Abstract
Facioscapulohumeral muscular dystrophy (FSHD), caused by partial deletion of the D4Z4 macrosatellite repeat on chromosome 4q, has a complex genetic and epigenetic etiology. To develop FSHD, D4Z4 contraction needs to occur on a specific genetic background. Only contractions associated with the 4qA161 haplotype cause FSHD. In addition, contraction of the D4Z4 repeat in FSHD patients is associated with significant D4Z4 hypomethylation. To date, however, the methylation status of contracted repeats on nonpathogenic haplotypes has not been studied. We have performed a detailed methylation study of the D4Z4 repeat on chromosome 4q and on a highly homologous repeat on chromosome 10q. We show that patients with a D4Z4 deletion (FSHD1) have D4Z4-restricted hypomethylation. Importantly, controls with a D4Z4 contraction on a nonpathogenic chromosome 4q haplotype or on chromosome 10q also demonstrate hypomethylation. In 15 FSHD families without D4Z4 contractions but with at least one 4qA161 haplotype (FSHD2), we observed D4Z4-restricted hypomethylation on chromosomes 4q and 10q. This finding implies that a genetic defect resulting in D4Z4 hypomethylation underlies FSHD2. In conclusion, we describe two ways to develop FSHD: (1) contraction-dependent or (2) contraction-independent D4Z4 hypomethylation on the 4qA161 subtelomere.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy
Lemmers, R. J. L. F., van der Vliet, P. J., Klooster, R., Sacconi, S., Camaño, P., Dauwerse, J. G., Snider, L., Straasheijm, K. R., Jan van Ommen, G., Padberg, G. W., et al. (2010) · Science · doi:10.1126/science.1189044 · Cited by 788
Self-citationFacioscapulohumeral Dystrophy: Incomplete Suppression of a Retrotransposed Gene
Snider, L., Geng, L. N., Lemmers, R. J. L. F., Kyba, M., Ware, C. B., Nelson, A. M., Tawil, R., Filippova, G. N., van der Maarel, S. M., Tapscott, S. J., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001181 · Cited by 503
Self-citationGeng, L. N., Yao, Z., Snider, L., Fong, A. P., Cech, J. N., Young, J. M., van der Maarel, S. M., Ruzzo, W. L., Gentleman, R. C., Tawil, R., et al. (2012) · Developmental Cell · doi:10.1016/j.devcel.2011.11.013 · Cited by 458
Self-citationTawil, R., Kissel, J. T., Heatwole, C., Pandya, S., Gronseth, G., & Benatar, M. (2015) · Neurology · doi:10.1212/wnl.0000000000001783 · Cited by 234
Self-citationDUX4 recruits p300/CBP through its C-terminus and induces global H3K27 acetylation changes
Choi, S. H., Gearhart, M. D., Cui, Z., Bosnakovski, D., Kim, M., Schennum, N., & Kyba, M. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw141 · Cited by 196
Metadata
- Authors
- de Greef, J. C., Lemmers, R. J. L. F., van Engelen, B. G. M., Sacconi, S., Venance, S. L., Frants, R. R., Tawil, R., & van der Maarel, S. M.
- Venue
- Human Mutation
- Publisher
- Hindawi Limited
- Published
- 2009-10
- Volume
- 30
- Issue
- 10
- Pages
- 1449-1459
- ISSN
- 1059-7794 (ISSN-L)
- 1098-1004
- OpenAlex
- W2075704285
- Cited by
- 217
- References
- 0
- FWCI
- 5.76
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHD. https://app.cochat.ai/papers/10.1002/humu.21091
- The paper
- de Greef, J. C., Lemmers, R. J. L. F., van Engelen, B. G. M., Sacconi, S., Venance, S. L., Frants, R. R., Tawil, R., & van der Maarel, S. M. (2009). Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHD. Human Mutation. https://doi.org/10.1002/humu.21091
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
